The research community at Memorial Sloan Kettering Cancer Center (MSKCC) is requesting a CyTOF mass cytometer (i.e. Cytometer via Time of Flight) manufactured by DVS Sciences to study phenotypic variability and heterotypic interactions in cancer biology and in immunology. CyTOF is an extension of traditional flow cytometry in which antibodies are tagged with chelated metal isotope and quantified by mass cytometry, thus circumventing the limitations of fluorescence emission that precludes measuring more than 10 or so parameters per single cell. The CyTOF methodology enables the acquisition of 30+ parameters per individual cell with a potential for 100 parameter-resolution. Incorporation of CyTOF into the Center's repertoire of technology platforms will provide investigators with an emerging technology that has the ability to transform our understanding of the complex signaling events that influence cell proliferation, differentiation and survival decisions, adaptaton of normal/cancer cells following therapy, and inter- and intra-tumoral heterogeneity. A team of researchers at MSKCC coalesced to apply single-cell heterogeneity analysis for mammalian cells. This group's research interests are diverse: S. Lowe studies tumor-suppressor and tumor maintenance networks; G. Altan-Bonnet develops new computational modeling methodologies to analyze lymphocytes' phenotypic variability; J. Joyce focuses on the tumor microenvironment; J. Massague studies regulatory networks involved in latent metastasis; S. Rudensky investigates regulatory T cell functions in complex inflammatory and tumor environments and M. van den Brink explores immune recovery and response to allogeneic hematopoietic stem cell transplantation. Other groups (Benezra, Levine, Park, Rosen, Sander, Wendel) study various aspects of tumor biology or therapy response. All these groups share an interest in testing the limits of single-cell resolution to better analyze how the phenotypic variability of immune/cancer cells drives the biology of the system. Moreover, measurements with multi-parametric single-cell resolution are critical to dissect heterotypic cell-cell interactions within these populations. CyTOF is the key technology that will deliver the necessary resolution. Of note, the MSKCC research team has already accumulated extensive expertise in single-cell phospho-profiling using fluorescence-based flow cytometry (Project I-IV), as well as some experience with the CyTOF technology (Project I). Moreover, the infrastructure at MSKCC is well-suited to incorporate mass cytometry, having a well-established core structure, including a flow cytometry core that will operate the machine, and antibody core that will assist with new antibody conjugations, a bioinformatics core that is well-suited to help analyze complex data sets arising from CyTOF studies, and a tissue procurement core that will facilitate the application of the technology on patient material. As the technology is new, there is no other source or alternative for its capabilities.